title: Laminin, gamma 2 (LAMC2): a promising new putative pancreatic cancer biomarker identified by proteomic analysis of pancreatic adenocarcinoma tissues.
abstract: In pancreatic cancer, the incidence and mortality curves coincide. One major reason for this high mortality rate in pancreatic ductal adenocarcinoma (PDAC) patients is the dearth of effective diagnostic, prognostic, and disease-monitoring biomarkers. Unfortunately, existing tumor markers, as well as current imaging modalities, are not sufficiently sensitive and/or specific for early-stage diagnosis. There is, therefore, an urgent need for improved serum markers of the disease. Herein, we performed Orbitrap® mass spectrometry proteomic analysis of four PDAC tissues and their adjacent benign tissues and identified a total of 2190 nonredundant proteins. Sixteen promising candidates were selected for further scrutiny using a systematic scoring algorithm. Our preliminary serum verification of the top four candidates (DSP, LAMC2, GP73, and DSG2) in 20 patients diagnosed with pancreatic cancer and 20 with benign pancreatic cysts, showed a significant (p < 0.05) elevation of LAMC2 in pancreatic cancer serum. Extensive validation of LAMC2 in healthy, benign, and PDAC sera from geographically diverse cohorts (n = 425) (Japan, Europe, and USA) demonstrated a significant increase in levels in early-stage PDAC compared with benign diseases. The sensitivity of LAMC2 was comparable to CA19.9 in all data sets, with an AUC value greater than 0.85 in discriminating healthy patients from early-stage PDAC patients. LAMC2 exhibited diagnostic complementarity with CA19.9 by showing significant (p < 0.001 in two out of three cohorts) elevation in PDAC patients with clinically low CA19.9 levels.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada;
authors.forename: Hari
authors.initials: H
authors.lastname: Kosanam
authors.forename: Ioannis
authors.initials: I
authors.lastname: Prassas
authors.forename: Caitlin C
authors.initials: CC
authors.lastname: Chrystoja
authors.forename: Ireena
authors.initials: I
authors.lastname: Soleas
authors.forename: Alison
authors.initials: A
authors.lastname: Chan
authors.forename: Apostolos
authors.initials: A
authors.lastname: Dimitromanolakis
authors.forename: Ivan M
authors.initials: IM
authors.lastname: Blasutig
authors.forename: Felix
authors.initials: F
authors.lastname: Rückert
authors.forename: Robert
authors.initials: R
authors.lastname: Gruetzmann
authors.forename: Christian
authors.initials: C
authors.lastname: Pilarsky
authors.forename: Masato
authors.initials: M
authors.lastname: Maekawa
authors.forename: Randall
authors.initials: R
authors.lastname: Brand
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism*; D005260:Female; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D040901:Proteomics
chemical_list: D014408:Biomarkers, Tumor; C400567:LAMC2 protein, human; D007797:Laminin